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Biomedical subjects

Natsuo Tachikawa

Publications and source records attributed to Natsuo Tachikawa.

12 recordsLinked to original sources
PubMed2006

Decrease in Epstein-Barr virus-positive AIDS-related lymphoma in the era of highly active antiretroviral therapy.

Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.

Adolescent↗
PubMed2006

Urinary beta2-microglobulin as a possible sensitive marker for renal injury caused by tenofovir disoproxil fumarate.

Tenofovir disoproxil fumarate (TDF) is renally excreted by a combination of glomerular filtration and active tubular secretion, and its renal safety profiles have been reported based on a limited increase of serum creatinine (sCr) levels. However, renal tubular function has not previously been well monitored. We measured sCr and urinary beta2-microglobulin (U-beta2MG) levels cross-sectionally in 70 patients treated with TDF [TDF+] and 90 patients on other antiretroviral therapy who had never been exposed to TDF [TDF-]. The mean U-beta2MG was significantly higher in TDF+ patients than that in TDF- patients (p < 0.0001), though no statistical difference was detected in their creatinine clearance estimated by using the Cockcroft-Gault equation. Multivariate analysis showed that coadministration of boosted lopinavir (LPV) and patients' body weight were associated with U-beta 2MG levels in TDF+ patients. U-beta2MG levels were significantly higher in those who also received boosted LPV [TDF+LPV+] (p = 0.0007), and abnormally high levels were noted in 67.7% of them. Furthermore, in the TDF+LPV+ group, U-beta2MG levels showed significant negative correlation with patients' body weight (p = 0.0029) and abnormal U-beta2MG was observed in all six patients with body weight less than 55 kg. In four patients, a rapid fall in U-beta2MG occurred after cessation of TDF. Relative to sCr, U-beta2MG could be a more sensitive marker of renal tubular injury caused by TDF. Boosted LPV co-administration and low body weight may be risk factors for TDF-induced renal tubular dysfunction, probably because these factors are associated with an increase in TDF concentration.

Adenine↗
PubMed2006

[HIV infection].

HIV infection can cause the destruction of cellular immunity. Highly active antiretroviral therapy (HAART) has strong effects to HIV-1 and usually consists of three to four anti-HIV-1 drugs. HAART has caused dramatic change of prognoses in HIV-1 patients. But HAART has several problems to be overcome. IFN-alpha/beta also has anti-HIV-1 effects and single usage of IFN can cause reduction of plasma HIV RNA viral load with about 1 log10 copies/ml after two to eight weeks. IFN can function as an additional anti-HIV-1 drug experimentally, especially to primary or early phase patients and patients with multiple drug resistances.

Anti-HIV Agents↗
PubMed2004

Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens.

Efavirenz (EFV) is metabolized by cytochrome P450 2B6 (CYP2B6) in the liver. We analyzed the genotypes of CYP2B6 and their contribution to plasma EFV concentrations in 35 EFV-treated patients in International Medical Center of Japan. The mean plasma EFV concentration of patients with CYP2B6 *6/*6 (Q172H and K262R) (25.4+/-7.5 microM, +/-SD, n = 2) was significantly higher than that of patients with genotypes *6 heterozygote (9.9+/-3.3 microM, n = 10) or without alleles *6 (8.0+/-2.6 microM, n = 23) (p < 0.0001). To confirm our result, we further analyzed nine patients (three with high EFV concentrations and arbitrarily selected six with normal EFV concentrations) treated in Osaka National Hospital, and it resulted that the only three patients with the high concentrations were the *6/*6 holder. EFV dose could be decreased in those patients harboring the genotype to reduce toxicity with compromising potency, representing the first step of the Tailor-Made therapy of HIV-1 infection.

Alkynes↗
PubMed2003

Primary nelfinavir (NFV)-associated resistance mutations during a follow-up period of 108 weeks in protease inhibitor naïve patients treated with NFV-containing regimens in an HIV clinic cohort.

BACKGROUND: Nelfinavir (NFV) is a widely prescribed HIV-1 specific protease inhibitor (PI). However, there are only a few reports that have described the long-term effects of NFV-containing regimens, especially with regard to the emergence of drug resistance in inner-city clinics. OBJECTIVES: The aim of this study was to investigate the clinical and virologic responses to treatment with NFV-containing regimens for up to 108 weeks and determine the timing and rate of emergence of primary NFV-resistance associated mutations in daily clinical practice. STUDY DESIGN: A cohort study in an inner-city clinic. Our study included 51 consecutive patients who were PI-nai;ve and commenced therapy in February 1997 through April 1999. RESULTS AND CONCLUSIONS: The proportions of patients who continued the same therapeutic regimen and showed virologic success (viral load <400 copies/ml) up to 108 weeks were 78 and 63%, respectively, based on intent-to-treat analysis. Among patients with a viral load persistently >400 copies/ml at week 12 (n=30), 11 developed primary NFV-resistance associated mutations by 108 weeks (stratified log-rank test; P<0.05). The Cox proportional hazard model showed that prior use of reverse transcriptase inhibitors (n=22) (relative hazard (RH); 2.10, 95% CI; 0.67-6.62), prior AIDS diagnosis (n=6) (RH; 1.70, 95% CI; 0.37-7.77), CD4 < 200/microl at baseline (n=19) (RH; 2.48, 95% CI; 0.78-7.81) and viral load >30,000 copies/ml at baseline (n=21) (RH; 2.10, 95% CI; 0.67-6.62) were not independent predictors of the NFV-resistance, although some tendency was noted. In total, 77% of the patients continued NFV-containing treatment without the NFV-resistance for 108 weeks. The viral load at week 12 could be used as a predictor of treatment success in our cohort study.

Adult↗
PubMed2003

[Comparison of pharmacokinetics of saquinavir soft-gel capsule (SQV-SGC) combined with ritonavir (RTV), SQV hard-gel capsule with RTV, and SQV-SGC alone].

Saquinavir (SQV) is a human immunodeficiency virus (HIV) specific protease inhibitor. When combined with ritonavir (RTV), plasma concentration of SQV is increased. In this study, we examined pharmacokinetics of SQV soft-gel capsule (SQV-SGC) 400 mg twice daily (BID) combined with RTV in HIV-1-infected patients (n = 4) and compared with those of SQV hard-gel capsule (SQV-HGC) 400 mg BID combined with RTV (n = 12). Pharmacokinetics of SQV-SGC 1,200 mg single dose in healthy subjects (n = 10) were also studied. Peak SQV concentration in plasma (Cmax) and area under the plasma concentration-time curve from 0 to 8 hour (AUC0-8 h) of SQV-SGC 400 mg BID combined with RTV group were higher than those of SQV-HGC 400 mg BID combined with RTV group; increase of 14.7% and 25.5%, respectively. Cmax and AUC0-8 h of SQV-SGC were higher than SQV-SGC 1,200 mg single dose group; increase of 3.9 fold and 8.5 fold, respectively. These results indicated that SQV-SGC combined with RTV therapy is the most potent antiviral effect among SQV-SGC with RTV, SQV-HGC with RTV, and SQV-SGC alone.

Anti-HIV Agents↗
PubMed2002

[Living donor liver transplantation in a patient with HIV].

Highly active anti-retroviral therapy(HAART) for human immunodeficiency virus(HIV) has delayed the disease progression. The advances prompted us to undertake liver transplantation in a 41-year-old man with hemophilia B, HIV infection, and hepatitis C(HCV) end-stage liver disease. The donor was the patient's elderly brother. His right liver was implanted by the standard method. Two months after the operation, interferon alfa and ribavirin were administered for HCV infection. HCV was eradicated two weeks after the treatment. The HIV viral load is persistently negative and HAART has not been started so far. Utilizing a organ from living relatives should be one of the options to resolve the concern around the utilization of a scarce public source from cadavers for patients who may not have an equivalent survival to HIV negative patients.

Adult↗
PubMed2001

Influence of human immunodeficiency virus type 1 infection on acute hepatitis A virus infection.

To assess the possible influence of human immunodeficiency virus type 1 (HIV-1) infection on the clinical course of acute hepatitis A virus (HAV) infection, 15 HIV-1-infected homosexual men and 15 non-HIV-infected age-matched subjects were compared. HAV load was higher in HIV-1-infected than in non-HIV-infected patients (P<.001). Duration of viremia in HIV-1-infected patients (median, 53 days) was significantly (P<.05) longer than in non-HIV-infected patients (median, 22 days). HIV-1-infected patients had lower elevations in alanine aminotransferase levels than did non-HIV-infected patients (P<.01) but had higher elevations in alkaline phosphatase levels than did non-HIV-infected patients (P<.001). Some HIV-1-infected patients still had HAV viremia when clinical symptoms had disappeared and alanine aminotransferase levels had returned to normal (60-90 days after the onset of symptoms). HIV-1 infection was associated with prolongation of HAV viremia, which might cause a long-lasting outbreak of HAV infection in HIV-1-infected homosexual men.

Acute Disease↗